Vaccination induces HIV broadly neutralizing antibody precursors in humans
Vaccination induces HIV broadly neutralizing antibody precursors in humans
复制标题
DOI：
10.1126/science.add6502
复制
发表时间：
2022-12-02
期刊：
影响因子：
56.9
通讯作者：
Schief, William R.
中科院分区：
文献类型：
--
作者：
Leggat, David J.;Cohen, Kristen W.;Schief, William R.
广谱中和抗体(BNAbs)可以预防艾滋病毒感染，但不能被人类疫苗诱导。诱导bNab的一个关键障碍是疫苗启动稀有的bNab前体B细胞。在一项随机、双盲、安慰剂对照的第1阶段临床试验中，HIV疫苗启动候选EOD-GT8 60mer辅以AS01B具有良好的安全性，在97%的疫苗接受者中诱导出VRC01型bNab前体，在血液中免疫球蛋白G B细胞中的中位数达到0.1%。BNab前体与bNAbs具有共同的性质，并获得了体细胞的超突变和与Boost的亲和力。这些结果建立了种系靶向疫苗启动概念的临床证据，支持开发增强方案来诱导bNAb，并鼓励将种系靶向策略应用于艾滋病毒和其他病原体的其他靶点。
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.